Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by
the CXCR4/SDF-1 axis

J 2016

Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis

PAVLASOVÁ, Gabriela, Marek BORSKÝ, Václav ŠEDA, Kateřina ČERNÁ, Jitka OSIČKOVÁ et. al.

Základní údaje

Originální název

Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis

Autoři

PAVLASOVÁ, Gabriela (203 Česká republika, domácí), Marek BORSKÝ (203 Česká republika, domácí), Václav ŠEDA (203 Česká republika, domácí), Kateřina ČERNÁ (203 Česká republika, domácí), Jitka OSIČKOVÁ (203 Česká republika, domácí), Michael DOUBEK (203 Česká republika, domácí), Jiří MAYER (203 Česká republika, domácí), Raffaele CALOGERO (380 Itálie), Martin TRBUŠEK (203 Česká republika, domácí), Šárka POSPÍŠILOVÁ (203 Česká republika, domácí), Matthew S. DAVIDS (840 Spojené státy), Thomas J. KIPPS (840 Spojené státy), Jennifer R. BROWN (840 Spojené státy) a Marek MRÁZ (203 Česká republika, garant, domácí)

Vydání

Blood, Washington DC, USA, American Society of Hematology, 2016, 0006-4971

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 13.164

Kód RIV

RIV/00216224:14740/16:00088920

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1182/blood-2016-04-709519

UT WoS

000385734800016

EID Scopus

2-s2.0-85015687470

Klíčová slova anglicky

CHRONIC LYMPHOCYTIC-LEUKEMIA; MARROW STROMAL CELLS; DOWN-REGULATION; PLUS RITUXIMAB; IN-VIVO; RECEPTOR; EXPRESSION; APOPTOSIS; ACTIVATION; BTK

Štítky

EL OK, podil, rivok

Změněno: 10. 1. 2017 15:06, Mgr. Eva Špillingová

Anotace

V originále

Agents targeting B-cell receptor (BCR) signaling-associated kinases such as Bruton tyrosine kinase (BTK) or phosphatidylinositol 3-kinase can induce mobilization of neoplastic B cells from the lymphoid tissues into the blood, which makes them potentially ideal to combine with anti-CD20 monoclonal antibodies (such as rituximab, obinutuzumab, or ofatumumab) for treatment of B-cell lymphomas and chronic lymphocytic leukemia (CLL). Here we show that interactions between leukemia cells and stromal cells (HS-5) upregulate CD20 on CLL cells and that administering ibrutinib downmodulates CD20(MS4A1) expression in vivo. We observed that CLL cells that have recently exited the lymph node microenvironment and moved into the peripheral blood (CXCR4(dim)CD5(bright) subpopulation) have higher cell surface levels of CD20 than the cells circulating in the bloodstream for a longer time (CXCR4(bright)CD5(dim) cells). We found that CD20 is directly upregulated by CXCR4 ligand stromal cell-derived factor 1 (SDF-1 alpha, CXCL12) produced by stromal cells, and BTK-inhibitor ibrutinib and CXCR4-inhibitor plerixafor block SDF-1 alpha-mediated CD20 upregulation. Ibrutinib also downmodulated Mcl1 levels in CLL cells in vivo and in coculture with stromal cells. Overall, our study provides a first detailed mechanistic explanation of CD20 expression regulation in the context of chemokine signaling and microenvironmental interactions, which may have important implications for microenvironment-targeting therapies.

Návaznosti

LD15144, projekt VaV

Název: Buněčné a nebuněčné základy pro regeneraci kostí a zubů (Akronym: TissueENG)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Buněčné a nebuněčné základy pro regeneraci kostí a zubů

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

NV16-29622A, projekt VaV

Název: VLIV TERAPEUTICKÉ INHIBICE BCR SIGNALIZACE NA GENOVOU EXPRESI U B BUNĚČNÝCH MALIGNIT A JEJÍ PROGNOSTICKÝ A PREDIKTIVNÍ VÝZNAM

Přiložené soubory

1363896.pdf

Požádat o autorskou verzi souboru

Citovat

PAVLASOVÁ, Gabriela, Marek BORSKÝ, Václav ŠEDA, Kateřina ČERNÁ, Jitka OSIČKOVÁ, Michael DOUBEK, Jiří MAYER, Raffaele CALOGERO, Martin TRBUŠEK, Šárka POSPÍŠILOVÁ, Matthew S. DAVIDS, Thomas J. KIPPS, Jennifer R. BROWN a Marek MRÁZ. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. Blood. Washington DC, USA: American Society of Hematology, 2016, roč. 128, č. 12, s. 1609-1613. ISSN 0006-4971. Dostupné z: https://dx.doi.org/10.1182/blood-2016-04-709519.

@article{1363896,
   author = {Pavlasová, Gabriela and Borský, Marek and Šeda, Václav and Černá, Kateřina and Osičková, Jitka and Doubek, Michael and Mayer, Jiří and Calogero, Raffaele and Trbušek, Martin and Pospíšilová, Šárka and Davids, Matthew S. and Kipps, Thomas J. and Brown, Jennifer R. and Mráz, Marek},
   article_location = {Washington DC, USA},
   article_number = {12},
   doi = {http://dx.doi.org/10.1182/blood-2016-04-709519},
   keywords = {CHRONIC LYMPHOCYTIC-LEUKEMIA; MARROW STROMAL CELLS; DOWN-REGULATION; PLUS RITUXIMAB; IN-VIVO; RECEPTOR; EXPRESSION; APOPTOSIS; ACTIVATION; BTK},
   language = {eng},
   issn = {0006-4971},
   journal = {Blood},
   title = {Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis},
   url = {http://www.bloodjournal.org/content/bloodjournal/128/12/1609.full.pdf},
   volume = {128},
   year = {2016}
}

TY  - JOUR
ID  - 1363896
AU  - Pavlasová, Gabriela - Borský, Marek - Šeda, Václav - Černá, Kateřina - Osičková, Jitka - Doubek, Michael - Mayer, Jiří - Calogero, Raffaele - Trbušek, Martin - Pospíšilová, Šárka - Davids, Matthew S. - Kipps, Thomas J. - Brown, Jennifer R. - Mráz, Marek
PY  - 2016
TI  - Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis
JF  - Blood
VL  - 128
IS  - 12
SP  - 1609-1613
EP  - 1609-1613
PB  - American Society of Hematology
SN  - 00064971
KW  - CHRONIC LYMPHOCYTIC-LEUKEMIA
KW  - MARROW STROMAL CELLS
KW  - DOWN-REGULATION
KW  - PLUS RITUXIMAB
KW  - IN-VIVO
KW  - RECEPTOR
KW  - EXPRESSION
KW  - APOPTOSIS
KW  - ACTIVATION
KW  - BTK
UR  - http://www.bloodjournal.org/content/bloodjournal/128/12/1609.full.pdf
L2  - http://www.bloodjournal.org/content/bloodjournal/128/12/1609.full.pdf
N2  - Agents targeting B-cell receptor (BCR) signaling-associated kinases such as Bruton tyrosine kinase (BTK) or phosphatidylinositol 3-kinase can induce mobilization of neoplastic B cells from the lymphoid tissues into the blood, which makes them potentially ideal to combine with anti-CD20 monoclonal antibodies (such as rituximab, obinutuzumab, or ofatumumab) for treatment of B-cell lymphomas and chronic lymphocytic leukemia (CLL). Here we show that interactions between leukemia cells and stromal cells (HS-5) upregulate CD20 on CLL cells and that administering ibrutinib downmodulates CD20(MS4A1) expression in vivo. We observed that CLL cells that have recently exited the lymph node microenvironment and moved into the peripheral blood (CXCR4(dim)CD5(bright) subpopulation) have higher cell surface levels of CD20 than the cells circulating in the bloodstream for a longer time (CXCR4(bright)CD5(dim) cells). We found that CD20 is directly upregulated by CXCR4 ligand stromal cell-derived factor 1 (SDF-1 alpha, CXCL12) produced by stromal cells, and BTK-inhibitor ibrutinib and CXCR4-inhibitor plerixafor block SDF-1 alpha-mediated CD20 upregulation. Ibrutinib also downmodulated Mcl1 levels in CLL cells in vivo and in coculture with stromal cells. Overall, our study provides a first detailed mechanistic explanation of CD20 expression regulation in the context of chemokine signaling and microenvironmental interactions, which may have important implications for microenvironment-targeting therapies.
ER  -

PAVLASOVÁ, Gabriela, Marek BORSKÝ, Václav ŠEDA, Kateřina ČERNÁ, Jitka OSIČKOVÁ, Michael DOUBEK, Jiří MAYER, Raffaele CALOGERO, Martin TRBUŠEK, Šárka POSPÍŠILOVÁ, Matthew S. DAVIDS, Thomas J. KIPPS, Jennifer R. BROWN a Marek MRÁZ. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. \textit{Blood}. Washington DC, USA: American Society of Hematology, 2016, roč.~128, č.~12, s.~1609-1613. ISSN~0006-4971. Dostupné z: https://dx.doi.org/10.1182/blood-2016-04-709519.

Přehled o publikaci